Linked Life Data

7764073

Source:http://linkedlifedata.com/resource/pubmed/id/7764073

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
1993-10-14
pubmed:abstractText
Although equipotent in terms of antiviral activity, the two enantiomers of 2'-deoxy-3'-thiacytidine (BCH 189) differ markedly in their cytotoxicity. (2'R-cis)-2'-deoxy-3'-thiacytidine (3TC) is substantially less toxic than its optical antipode, and is undergoing development for the therapy of HIV infection. Cytidine deaminase from Escherichia coli is shown here to deaminate 2'-deoxy-3'-thiacytidine enantioselectively to leave 3TC essentially optically pure. This reaction has been used to develop a process for production of 3TC in multikilogram amounts. The production of cytidine deaminase was enhanced by strain improvement, fermentation development, and finally by cloning and overexpression of the gene. The enzyme was immobilized on Eupergit-C, which allowed it to be reused many times. The biotransformation conditions were optimized so that the best use could be made of the catalyst. A robust scaleable product isolation process was developed to yield the crystalline product. Overall, yields through the resolution process of 76% were obtained. All aspects of this process are capable of substantial further scaleup with only minor modifications.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
B
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0141-0229
pubmed:author
pubmed:issnType
Print
pubmed:volume
15
pubmed:geneSymbol
cdd
pubmed:owner
NLM
pubmed:authorsComplete
N
pubmed:pagination
749-55
pubmed:dateRevised
2001-11-13
pubmed:meshHeading
pubmed:year
1993
pubmed:articleTitle
Enzymatic production of optically pure (2'R-cis)-2'-deoxy-3'-thiacytidine (3TC, lamivudine): a potent anti-HIV agent.
pubmed:affiliation
Department of Natural Products Discovery, Glaxo Group Research Ltd, Greenford, Middlesex, England.
pubmed:publicationType
Journal Article